Intellia Begins HAELO Phase 3 Trial of NTLA-2002 for Hereditary Angioedema

Intellia Therapeutics, Inc. has announced the launch of the HAELO Phase 3 clinical trial for NTLA-2002, a cutting-edge gene-editing therapy aimed at treating hereditary angioedema (HAE). This pivotal study marks a significant progression for NTLA-2002, which is designed as a single-dose treatment for preventing the life-threatening swelling attacks associated with HAE.

Following the successful completion of Phase 2 trials and the approval of an Investigational New Drug Application amendment by the U.S. Food and Drug Administration (FDA), patient screening for the Phase 3 trial has commenced. John Leonard, M.D., President and CEO of Intellia, emphasized the importance of this milestone, stating that the treatment has shown promising results in early trials, potentially offering a complete response with no further attacks or ongoing treatment required.

The HAELO Phase 3 trial is a global, randomized, double-blind, placebo-controlled study aimed at assessing the efficacy and safety of NTLA-2002 in 60 adult patients with Type I or Type II HAE. Participants will be randomly assigned in a 2:1 ratio to receive either a single 50 mg infusion of NTLA-2002 or a placebo. Those in the placebo group will have the option to crossover to NTLA-2002 treatment at week 28. The primary goal of the study is to measure the change in the frequency of HAE attacks from week 5 through week 28.

This progression to Phase 3 is based on positive outcomes from the ongoing Phase 1/2 study (NCT05120830) of NTLA-2002. The interim results from the Phase 1 trial revealed significant reductions in attack rates and sustained decreases in kallikrein levels, a key protein involved in HAE. Detailed results from the Phase 2 portion are scheduled to be presented at the 2024 American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting in Boston, Massachusetts.

NTLA-2002 is based on the revolutionary CRISPR/Cas9 gene-editing technology, which earned a Nobel Prize. The treatment works by inactivating the KLKB1 gene, responsible for producing prekallikrein, a precursor to the kallikrein protein involved in HAE attacks. The therapy has received several regulatory recognitions, including Orphan Drug and RMAT Designations from the FDA, an Innovation Passport from the U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA), and Priority Medicines (PRIME) Designation from the European Medicines Agency, as well as Orphan Drug Designation from the European Commission.

Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable and severe inflammatory attacks that can affect various organs and tissues, leading to significant pain and potential life-threatening situations. It is estimated to affect one in 50,000 individuals. While current treatments are available to manage the condition, they often require chronic administration and may not completely prevent breakthrough attacks. Traditional therapies can involve frequent intravenous or subcutaneous administration, sometimes as often as twice per week, or daily oral doses to maintain disease control. Inhibiting kallikrein has been validated as an effective strategy for preventing HAE attacks.

Intellia Therapeutics is a leader in the clinical-stage gene-editing field, focusing on CRISPR-based therapies to transform medicine. The company’s in vivo programs aim to precisely edit disease-causing genes within the human body, while its ex vivo programs engineer human cells outside the body to treat conditions like cancer and autoimmune diseases. Intellia continues to advance its CRISPR platform, seeking to expand its capabilities with innovative editing and delivery technologies.